Flavopiridol induces BCL-2 expression and represses oncogenic transcription factors in leukemic blasts from adults with refractory acute myeloid leukemia.

Abstract	Flavopiridol is a cyclin-dependent kinase inhibitor that induces cell cycle arrest, apoptosis, and clinical responses in selected patients with acute myeloid leukemia (AML). A better understanding of the molecular pathways targeted by flavopiridol is needed to design optimal combinatorial therapy. Here, we report that in vivo administration of flavopiridol induced expression of the BCL-2 anti-apoptotic gene in leukemic blasts from adult patients with refractory AML. Moreover, flavopiridol repressed the expression of genes encoding oncogenic transcription factors (HMGA1, STAT3, E2F1) and the major subunit of RNA Polymerase II. Our results provide mechanistic insight into the cellular pathways targeted by flavopiridol. Although further studies are needed, our findings also suggest that blocking anti-apoptotic pathways could enhance cytotoxicity with flavopiridol.
Authors	Dwella M Nelson, Biju Joseph, Joelle Hillion, Jodi Segal, Judith E Karp, Linda M S Resar
Journal	Leukemia & lymphoma (Leuk Lymphoma) Vol. 52 Issue 10 Pg. 1999-2006 (Oct 2011) ISSN: 1029-2403 [Electronic] United States
PMID	21728742 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Antineoplastic Agents Apoptosis Regulatory Proteins Flavonoids Piperidines Protein Kinase Inhibitors Proto-Oncogene Proteins c-bcl-2 Transcription Factors alvocidib RNA Polymerase II
Topics	Adult Antineoplastic Agents Apoptosis Regulatory Proteins Blast Crisis (drug therapy) Female Flavonoids (administration & dosage, pharmacology, therapeutic use) Humans Leukemia, Myeloid, Acute (drug therapy, pathology) Male Middle Aged Oncogenes Piperidines (administration & dosage, pharmacology, therapeutic use) Protein Kinase Inhibitors Proto-Oncogene Proteins c-bcl-2 (biosynthesis, drug effects) RNA Polymerase II (drug effects) Transcription Factors (antagonists & inhibitors) Young Adult

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